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First published online 15 March 2005
doi: 10.1242/jcs.02278

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Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells

¹ Department of Pharmacology, Wayne State University, School of Medicine, Detroit, MI 48201, USA
² Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA

^* Author for correspondence (e-mail: dcavallo{at}med.wayne.edu)

Accepted 20 January 2005

Cathepsin B and pro-urokinase plasminogen activator (pro-uPA) localize to the caveolae of HCT 116 human colorectal carcinoma cells, an association mediated by active K-RAS. In this study, we established a stable HCT 116 cell line with a gene encoding antisense caveolin-1 (AS-cav-1) to examine the effects of caveolin-1, the main structural protein of caveolae, on the expression and localization of cathepsin B and pro-uPA, and their cell-surface receptors p11 and uPA receptor (uPAR), respectively. AS-cav-1 HCT 116 cells secreted less procathepsin B than control (empty vector) cells as measured by immunoblotting and pepsin activation of the proenzyme. Expression and secretion of pro-uPA was also downregulated in AS-cav-1 HCT 116 cells. Localization of cathepsin B and pro-uPA to caveolae was reduced in AS-cav-1 HCT 116 cells, and these cells expressed less total and caveolae-associated p11 and uPAR compared with control cells. Previous studies have shown that uPAR forms a complex with caveolin-1 and ß1-integrin, and we here show that downregulation of caveolin-1 also suppressed the localization of ß1-integrin to caveolae of these cells. Finally, downregulation of caveolin-1 in HCT 116 cells inhibited degradation of the extracellular matrix protein collagen IV and the invasion of these cells through Matrigel. Based on these results, we hypothesize that caveolin-1 affects the expression and localization of cathepsin B and pro-uPA, and their receptors, thereby mediating cell-surface proteolytic events associated with invasion of colon cancer cells.

Key words: Colorectal carcinoma, Caveolin-1, Proteases, Proteolysis, Invasion

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